Prd1 associates with the clathrin adaptor α-Adaptin and the kinesin-3 Imac/Unc-104 to govern dendrite pruning in Drosophila

摘要

Refinement of the nervous system depends on selective removal of excessive axons/dendrites, a process known as pruning. Drosophila ddaC sensory neurons prune their larval dendrites via endo-lysosomal degradation of the L1-type cell adhesion molecule (L1-CAM), Neuroglian (Nrg). Here, we have identified a novel gene, pruning defect 1 ( prd1 ), which governs dendrite pruning of ddaC neurons. We show that Prd1 colocalizes with the clathrin adaptor protein α-Adaptin (α-Ada) and the kinesin-3 immaculate connections (Imac)/Uncoordinated-104 (Unc-104) in dendrites. Moreover, Prd1 physically associates with α-Ada and Imac, which are both critical for dendrite pruning. Prd1, α-Ada, and Imac promote dendrite pruning via the regulation of endo-lysosomal degradation of Nrg. Importantly, genetic interactions among prd1 , α-adaptin , and imac indicate that they act in the same pathway to promote dendrite pruning. Our findings indicate that Prd1, α-Ada, and Imac act together to regulate discrete distribution of α-Ada/clathrin puncta, facilitate endo-lysosomal degradation, and thereby promote dendrite pruning in sensory neurons. Author summary During the maturation of the nervous system, some neurons can selectively eliminate their unnecessary connections, including dendrites and axons, to retain specific connections. In Drosophila , a class of sensory neurons lose all their larval dendrites during metamorphosis, when they transition from larvae to adults. We previously showed that these neurons prune their dendrites via lysosome-mediated degradation of a cell-adhesion protein, Neuroglian. In this paper, we identified a previously uncharacterized gene, pruning defect 1 ( prd1 ), which plays an important role in dendrite pruning. We show that Prd1 is localized and complexed with α-Adaptin and Imac, two other proteins that are also essential for dendrite pruning. Moreover, Prd1, α-Adaptin, and Imac act in a common pathway to promote dendrite pruning by down-regulating Neuroglian protein. Thus, our study highlights a mechanism whereby Prd1, α-Adaptin, and Imac act together to regulate distribution of α-Adaptin/clathrin puncta, facilitate lysosome-dependent protein degradation, and thereby promote dendrite pruning in Drosophila sensory neurons.